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Ubiquitination is a key regulatory mechanism which attaches ubiquitin, a small protein modifier, to protein substrates, thereby modifying their structure, function, cellular location or targeting them for destruction via proteolysis. Inappropriate regulation of ubiquitination pathways is linked with a number of human diseases. In recent years, components of these pathways have emerged as a new and relatively untapped class of targets for drug discovery, with applications in cancer, neurodegenerative disorders such as Alzheimer's and Parkinson's disease, viral infection, diabetes, and inflammation.
In 2011, we began applying our protein expression and purification expertise to bring active E1, E2 and E3 ubiquitin enzyme products and services to the market. With over 20 functional ubiquitination pathways created already, we are helping to make this emerging target class become more accessible for drug discovery.
Eurofins has removed the complexity of ubiquitination studies by providing functionally active ubiquitin cascades, making the pathway readily accessible for research and drug discovery. Our assay guides include protocols for measuring activity by ELISA, electrochemiluminescence immunoassay, and Western blot. All of our enzymes are available in multiple pack sizes, including 10 μg, 250 μg or bulk (1 mg and greater), to provide you with flexible options from a one-time experiment to a full-blown HTS campaign.
Advantages of our ubiquitin enzymes and substrates:
Figure 1. Ubiquitination Pathway
The ubiquitination pathway consists of three sequential steps: 1) an ATP dependent step of loading E1 activating enzyme with ubiquitin, 2) transfer of the E1's ubiquitin to an E2 conjugating enzyme and 3) the E3 ligase-mediated transfer of ubiquitin from an E2 to the substrate. This process can be repeated to polyubiquinate a substrate, leading to its proteasome-mediated degradation, whereas monoubiquit;inated targets (e.g., cell surface receptors) will have altered signaling properties.
Figure 2. Schematic of the SCF-Skp2/Cks1 Ubiquitination Cascade.
The active complexes depicted are all available in our catalogue, including E3 ligase complex (full-length Rbx1, Cul1, Skp1, Skp2, and Cks1), substrate complex (full-length p27, Cyclin E, and Cdk2), E2 enzyme UbcH3, and E1 enzyme UBE1.